Effect of cold stress on ovarian & uterine microcirculation in rats and the role of endothelin system

Abstract

Background: Cold, an environmental factor, induces many reproductive diseases. It is known that endothelin (ET) is a potent vasoconstrictor, and cold stress can increase the expression of ET and its receptors. The cold stress rat model was developed to examine two parameters: (1) the effects of cold stress on ovarian and uterine morphology, function, and microvascular circulation and (2) possible mechanisms of ET and its receptors involved in cold stress-induced menstruation disorders. Methods: The rat cold stress model was prepared with an ice water bath. The estrous cycle was observed by methylene blue and hematoxylin and eosin (H&E) staining. Serum estradiol 2 (E 2), testosterone (T), progesterone (P) were detected by radioimmunoassay. Hemorheology indices were measured. The real-time blood flow of auricle and uterine surfaces was measured. Expressions of CD34 and α-SMA in ovarian and uterine tissues were detected by immunohistochemistry. ET-1 contents in serum were tested, and expressions of ET-receptor types A and B (ET-AR and ET-BR) in ovarian tissues were detected via Western blotting. Results: Cold stress extended the estrous cycle, thereby causing reproductive hormone disorder, imbalance of local endothelin/nitric oxide expression, and microcirculation disturbance. Cold-stress led to up-regulation of ET-AR expression and protein and down-regulation of ET-BR expression in rats. Conclusions: This study suggests that the reason for cold stress-induced dysfunction in reproductive organs may be closely related to the imbalance of ET-1 and its receptor expressions, leading to microvascular circulation disorders in local tissues.

Long-term intermittent cold exposure affects peri-ovarian adipose tissue and ovarian microenvironment in rats

“…The changes that occur in the POAT after browning and the effects of these changes on the peri-ovarian microenvironment, the ovarian microenvironment, and ovarian function have not been explored. We found that after POAT browning, the expression levels of APDN, Lep, and AMPK were significantly increased, similar to the effects observed during iWAT browning [ 9 , 32 ]. Our results suggested that the peri-ovarian microenvironment changes along with POAT browning.…”

“…Cold exposure has adverse effects on the female reproductive system [ 4 – 6 ], affecting ovarian [ 7 ] and uterine [ 4 ] functions and hormone secretion [ 8 ]. Possible reasons include: imbalance of ET-1 and its receptor expression leads to local tissue microvascular circulatory disturbances [ 9 ]; affects follicular development by activating sympathetic nerve activity in the ovary [ 10 , 11 ]; Cold stress can also cause reproductive hormone disorders, causing uterine arteries to contract, resulting in reduced blood flow [ 12 ]. However, the exact mechanisms through which these changes occur have not been well-elucidated.…”

Unraveling the Mystery of Cold Stress-Induced Myocardial Injury

“…It is reported that ET-1 is a local hormone whose secretion varies according to changes in the surrounding environment. Cold exposure increases the secretion of ET in plasma and increase in ET-1 in the heart tissue ( Chen and Sun, 2006 ; Barton and Yanagisawa, 2008 ; Wang D. et al, 2020 ). ET-1 plays an important role in the regulation of cardiac growth, myocardial contractility, and hemodynamics, and also leads to pathological myocardial hypertrophy by activating phosphoinositide 3-kinases (PI3Ks)/Akt pathway related to myocardial contractility and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinases (ERK1/2) pathway related to cell hypertrophy ( Drawnel et al, 2013 ; Takano et al, 2020 ).…”

Chronic Stress Detrimentally Affects In Vivo Maturation in Rat Oocytes and Oocyte Viability at All Phases of the Estrous Cycle

“…It is also well-known that temperature alterations, either hot [ 37 ] or cold [ 11 ], cause adverse effects on the reproductive system. It has recently been reported that cold stress (0–1 °C) lengthened the estrous cycle in rats and reduced testosterone, E 2 , and progesterone levels, leading to reproductive organ dysfunction [ 38 ]. Additionally, restraint stress caused apoptosis in cumulus cells, reducing the oocyte developmental potential to the blastocyst stage [ 39 ].…”